Background: Dual diagnosis (DD), defined as the co-occurrence of a substance use disorder (SUD) and a severe mental illness (SMI), is associated with several negative outcomes. Typical antipsychotics (TAP) are not of great value for patients with DD as they are associated with poorer responses and can worsen SUD. Atypical antipsychotics (AAP) offer several advantages compared to TAP and in DD patients they have been found to be effective in treating both, psychiatric symptoms and substance use. The aim of this article is to review the use of clozapine (CLO) for treating DD patients.
Methods: A search of MEDLINE, EMBASE and Pubmed was performed in order to identify publications that examined the use of CLO in the treatment of DD.
Results: There is consistent data in regard to the efficacy of CLO in the treatment of DD patients in both studies with and without comparison to TAP and other AAP. These positive results have been found for different substances of abuse and in different SMI. However, there is a lack of randomized, placebo-controlled trials in this field.
Conclusions: CLO has been found to be at least as effective as TAP and other AAP in treating psychiatric symptoms, but it has shown itself to be more effective in reducing substance use in DD patients. Several hypotheses have been proposed to explain this effectiveness: 1) amelioration of reward system dysfunction in the dopamine-mediated mesocorticolimbic circuits; 2) improvement of negative symptoms, and relief of anxiety, depression and dysphoria; 3) improvement of cognitive dysfunction associated with DD; and 4) reduction of craving. CLO might be considered as a pharmacological agent for use in patients with DD, although safety issues, such as the risk of agranulocytosis and seizures must be taken into account. Even though there is a growing body of evidence suggesting the beneficial effects of CLO in DD patients, further randomized, blind, controlled trials, with larger sample sizes and longer follows-up are needed.